Characterization of rhesus cytomegalovirus genes associated with anti-viral susceptibility.
Studies were initiated to determine whether rhesus cytomegalovirus (RhCMV)-infected macaques could serve as an animal model for evaluating anti-CMV compounds, as macaques have a naturally occurring CMV that is similar to human CMV (HCMV). Utilizing plaque reduction assays, RhCMV was tested to anti-viral susceptibility. By these assays. RhCMV displayed anti-viral susceptibility to ganciclovir at a 50% effective dose (ED50) of 0.8 microM, acyclovir at an ED50 of 15 microM, and foscarnet at an ED50 of 250 microM. By Southern blot analysis with HCMV-UL97 (phosphotransferase) and DNA polymerase (pol) genes as probes, we isolated viral DNA fragments that strongly hybridized. DNA sequence analysis of these DNA fragments revealed two open reading frames with homology to HCMV UL97 and DNA polymerase. Steady-state RNA analysis revealed that the RhCMV UL97 homologue and pol genes are transcribed as early late and early genes, respectively. Comparison against HCMV showed the RhCMV UL97 homologue exhibits 54.4% amino acid (aa) sequence identity to HCMV UL97 and the RhCMV DNA polymerase 59.2% aa sequence identity to HCMV DNA polymerase. Results from anti-viral assays and molecular characterization of these two viral genes suggest that RhCMV-infected rhesus macaques should serve as an excellent animal model for evaluating future anti-CMV compounds.
Swanson
R
R
Division of Pathobiology and Immunology, Oregon Regional Primate Research Center, Beaverton 97006, USA.
Bergquam
E
E
Wong
S W
SW
D000212:Acyclovir / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects; D015774:Ganciclovir / Q000494:pharmacology*; D015751:Genes, pol / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta / Q000821:virology; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000998:Antiviral Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase; D015774:Ganciclovir; D000212:Acyclovir